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- A diabetic who injects too much insulin can lose consciousness. Explain how injecting excess insulin can impair brain function. Explain also why an injection of glucagon can restore normal function.A diabetic who injects too much insulin can lose consciousness. Explain why injecting excess insulin could impair brain function. Glucagon reverses this effect. Explain how.WA 82. Regulation of cellular metabolism by insulin requires activation of the insulin-receptor substrate protein-1 (IRS1). Some individuals who have type 2 diabetes mellitus have mutations in the IRS1 gene. Which of the following normal steps in insulin signaling is most likely to be impaired by these mutations? A) Cleavage of IRS1 by the insulin receptor B) Phosphorylation of IRS1 by the insulin receptor C) Production of inositol 1,4,5-trisphosphate by IRS1 D) Stimulation of a G protein by IRS1 E) Synthesis of diacylglycerol by IRS1
- 6. A. List all of the ionizable functional groups that are found in insulin when in aqueous solution. List which amino acid residues have these ionizable groups and list all of the pka and pKb values (including the R groups) that are on both polypeptide chains that make up insulin. (see the table at the end of this HW set; note that tyrosine and cysteine both have unusual pka's, since these side groups ionize above the pKR's given to have a negative charge). B. The isoelectric point of insulin is reported to be around 5.3-5.35. Using the method covered in class, estimate the isoelectric point of insulin and compare your answer to the values above. C. For a polypeptide to be soluble in an aqueous solution, is it good to be near the isoelectric point? Why or why not? Notes: a couple of unusual R group's that ionize (cysteine and tyrosine have R groups that have pka values; histidine has a pkb). The table at the end of this homework set (also in the lecture notes) lists the pka's and…8. In patients with diabetes mellitus type I, the biochemical disorders result from changes in fucl metabolism. One of these signs is acidosis. Explain why such patients have a deviation of blood pH from the norm? For this me the Ocuics, name d) specify the hormone that accelerates this preeursor formation and provide appropriate charts, starting from the hormone binding to adipocyte and concluding with precursor formation, give an explanation to the charts.Endocrine & Signalling 26. HO- NH2 HO- The molecule above is a hormone. Select FOUR statements that are correct with regard to this moelcule below. This is the least active form of this hormone There is another more active form of this hormone This molecule is derived from tyrosine This hormone stimulates fat metabolism Biosynthesis of this molecule requires iodine This molecule is a tryptophan metabolite This hormone targets two specific receptors This hormone stimulates fat storage This molecule is derived from cholesterol This hormone is synthesised in the adrenals
- Diabetes mellitus is characterized by insufficiency of thepancreas to produce enough insulin to regulate the blood sugarlevel. In type I diabetes, the pancreas produces no insulin, andthe patient is totally dependent on insulin from an externalsource to be infused at a rate to maintain blood sugar levelsat normal levels. Hyperglycemia occurs when blood glucoselevel rises much higher than the norm (>8 mmol/L) for pro-longed periods of time; hypoglycemia occurs when the blood sugar level falls below values of 3 mmol/L. Both situations canbe deleterious to the individual’s health. The normal range ofblood sugar is between 3.8 and 5.6 mmol/L, the target rangefor a controller regulating blood sugar.A patient with type I diabetes needs your help to maintainher blood sugar within an acceptable range (3 mmol/L<glucose<8 mmol/L). She has just eaten a large meal (a disturbance) that you estimate will release glucose accord-ing toD(t)=0.5e−0.05t,wheretis in minutes andD(t)is inmmol/L –…1. Where is insulin synthesised and in what form is it stored in the body?2. Describe the mechanism of release of insulin into the bloodstream.Lantus differs from "normal" insulin in that: Select one: Oa. The usual insulin molecule has been combined with zinc isophane Ob. A glycine has been substituted in at A21, and two new arginines have been added as B31 and B32 *. An aspartic acid has been substituted for proline at B28 Od. A "C-peptide" chain has been added Oe The proline at B28 and the lysine at B29 have been reversed
- 28. functional insulin required the association of two polypeptides known as the A and B chainsNovolog differs from "normal" insulin in that: Select one: a. An aspartic acid has been substituted for proline at B28 b. The proline at B28 and the lysine at B29 have been reversed c. A glycine has been substituten in at A21, and two new arginines have been added as B31 and B32 d. A "C-peptide" chain has been added e. The usual insulin molecule has been combined with zinc isophaneDiscuss the following statement: “We wouldhave no idea today of the importance of insulin as a reg-ulatory hormone if its absence were not associated withthe human disease diabetes. It is the dramatic conse-quences of its absence that focused early efforts on theidentification of insulin and the study of its normal role inphysiology.”